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Hypotonia-induced cell swelling enhances ultrasound-induced mechanical damage to cancer cells

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Abstract

Introduction

It has been shown that killing of suspended cells by low-intensity ultrasound (0.08–0.11 W/cm2) can be enhanced by a mild non-lethal hypotonic (146 mOsm) medium.

Purpose

In this study we wished to determine whether hypotonia-induced cell swelling of suspension cells was directly related to enhancement of ultrasound-mediated cell killing, and to verify whether similar effects could be observed on circulating and attached cells.

Methods

U937 cells under mild hypotonia were exposed to ultrasound for different times with real-time monitoring of cell size using a particle-size-distribution analyzer. To study the effect on attached cells, HeLa cells were exposed to ultrasound while under hypotonia in an in vivo-simulated set-up.

Results

The result showed that the enhanced cell killing (up to more than twice) was directly proportional to hypotonia-induced cell swelling. Similar membrane damage based on PI staining could be observed on HeLa cells treated with hypotonia. An in vivo-simulated circulating system also showed similar findings for hypotonia-enhanced ultrasound cell killing.

Conclusion

These findings showed that mild hypotonia can be used to augment the effect of ultrasound in the treatment of cancers, particularly leukemia. The results showing that such enhancement is related to cell swelling could guide us toward proper timing of sonication while under hypotonic treatment.

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Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas (18800075 and 20500432) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and also in part by a grant from Fukuoka University Central Research Institute. We would like also to thank Mr Yasser Ilich F. Loayon for assisting with some of the experiments.

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Authors and Affiliations

  1. Department of Anatomy, Fukuoka University School of Medicine, Fukuoka, 814-0180, Japan

    Loreto B. Feril Jr., Katsuro Tachibana, Kazuki Yamaguchi, Koichi Ogawa, Hitomi Endo, Yutaka Irie & Yoshimi Harada

  2. Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan

    Takashi Kondo, Ryohei Ogawa & Qing-Li Zhao

Authors
  1. Loreto B. Feril Jr.
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  2. Katsuro Tachibana
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  3. Takashi Kondo
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  4. Ryohei Ogawa
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  5. Qing-Li Zhao
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  6. Kazuki Yamaguchi
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  7. Koichi Ogawa
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  8. Hitomi Endo
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  9. Yutaka Irie
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  10. Yoshimi Harada
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Corresponding author

Correspondence to Loreto B. Feril Jr..

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Feril, L.B., Tachibana, K., Kondo, T. et al. Hypotonia-induced cell swelling enhances ultrasound-induced mechanical damage to cancer cells. J Med Ultrasonics 37, 3–8 (2010). https://doi.org/10.1007/s10396-009-0241-3

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  • DOI: https://doi.org/10.1007/s10396-009-0241-3

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